First kidney from stem cells

Researchers grow a protoniere directly from induced stem cells

Part of the protoniere grown from induced stem cells. The different colors represent different cell types and structures. © Fabian Fromling and Minoru Takasato
Read out

Organ from the test tube: Researchers have succeeded for the first time in breeding a kidney precursor directly from induced stem cells. The organoid already contains the typical renal tubules and is similar to the kidney of an early embryo. The protoniere can even filter, as the researchers report in the journal "Nature". This is an important step towards a transplantable kidney from the laboratory.

The kidneys are vital for the purification of our blood. If they do not work properly, only blood dialysis or transplantation remains. But donor organs are rare and dialysis can only partially replace kidney function. That's why researchers have been looking for ways to grow kidneys in the lab for some time. But a kidney is relatively complicated: it consists of more than 20 different cell types and complex fine structures.

In 2013, US scientists succeeded in regenerating a dead rat kidney so that it became a functioning organ again. The kidney thus created actually began its work - albeit with limited efficiency. In 2012 another research team of embryonic kidney cells had bred a type of anterior kidney with two of the most important kidney cell types.

From stem cells to the organoid

So far, however, the crucial first step was missing: the production of renal progenitor cells from induced stem cell cells, which were returned from adult somatic cells back to the undifferentiated state. This has now succeeded Minoru Takasato of the University of Queensland in St. Lucia and his colleagues. They first identified the growth factors that cause pluripotent stem cells to become kidney cell progenitors. As it turned out, a finely tuned sequence of, above all, two chemicals is necessary.

The laboratory-bred protoniere is similar to that of an early embryo. © Minoru Takasato

The researchers used this knowledge to grow stem cells first into the precursor cells and then into a first kidney an organoid in which a network of renal canals with nephrons already existed, as well as first approaches connective tissue and blood vessel precursors. "All of these kidney components were formed, formed fine structures and matured, " report Takasato and his colleagues. display

Protoniere is already functional

The grown organoids and the gene expression of their individual cell types thus resembled the kidneys of an embryo in the first trimester of pregnancy. "Each renal organoid reached the substantial size of 500 nephrons, which corresponds to a mammal 14.5 days after fertilization of the egg, " said the researchers.

This protoniere was even functional, as another experiment proved. The researchers added a fluorescently labeled sugar molecule to the culture and were able to observe how the renal canals picked up these molecules. If, instead, the cytotoxin, which mainly acts on the kidney, was administered cisplatin, the nephron cells died. This shows that these cells responsible for the blood filtration enriched the poison from the nutrient solution and then perished.

"An important step"

Even if this organoid is not yet a complete kidney, it represents a further step towards functioning substitute organs "from the test tube". "It's still a long way to clinically useful, transplantable kidneys, " says Jamie Davies of the University of Edinburgh in an accompanying commentary. "But the protocol developed by Takasato and his colleagues is a valuable step in the right direction."

And, of course, such precursors could already be: using them in drug tests can save animal testing. In addition, replacement cells can be obtained from brothed organoids for various cell therapies, as the researchers explain. (Nature, 2015; doi: 10.1038 / nature15695)

(Nature, 08.10.2015 - NPO)